close

Вход

Забыли?

вход по аккаунту

?

Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A.

код для вставкиСкачать
Elevated Expression of Messenger RNA for
Peripheral Myelin Protein 22 in Biopsied
Peripheral Nerves of Patients with
Charcot-Marie-Tooth Disease Type 1A
Hiroo Yoshikawa, MD,* Tomoya Nishimura, MD,* Yuji Nakatsuji, MD," Harutoshi Fujimura, MD,"
Masato Himoro, MD,t Kiyoshi Hayasaka, MD,? Saburo Sakoda, MD," and Takehiko Yanagihara, MD"
The human peripheral myelin protein 22 (PMP-22) gene has been mapped to chromosome 1 7 ~ 1 1 . 2in the duplicated
region associated with Charcot-Marie-Tooth disease type 1A. Southern blot analysis using PMP-22 as a probe indicated
that the PMP-22 gene was duplicated in 5 patients from unrelated Japanese families with Charcot-Marie-Tooth disease
type 1. I n order to investigate wliether or not an extra copy of PMP-22 has an effect on its gene expression, we
analyzed relative expression of messenger RNA for PMP-22 and protein 0 (PO) against beta-actin by Northern blotting
in biopsied nerves of the patients with type 1A disease, and compared the results with those of patients having other
demyelinating neuropathies and the autopsied nerves of patients without neuropathies. The relative expression of
PMP-22 messenger RNA in 5 patients with Charcot-Marie-Tooth disease type 1A was significantly higher than that
in 5 patients with other demyelinating neuropathies ( p < 0.05). There was no statistically significant difference in W
expression between them. This study provided direct evidence for elevated expression of PMP-22 in peripheral nerves
of patients with Charcot-Marie-Tooth disease type 1A as the result of a gene dosage effect. However, the relation
between elevated expression of PMP-22 and the mechanism causing demyelination remains undetermined.
Yoshikawa H, Nishimura T, Nakatsuji Y. Fujimura H, Himoro M, Hayasaka K, Sakoda S, Yanagihara T.
Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves
of patients with Charcot-Marie-Tooth disease type IA. Ann Neurol 1994;35:445-450
Charcot-Marie-Tooth disease type 1 (CMT1) is an
inherited demyelinating peripheral neuropathy that
causes chronic progressive distal muscle atrophy and
sensory impairment [ 11. Although autosornal recessive,
X-linked, or sporadic transmission has been reported,
most pedigrees demonstrate autosomal dominant inheritance 121. Autosomal dominant forms are known
to map to chromosome 17 (CMTlA) 13, 41, chromosome 1 (CMTIB) IS, 61, and another unknown autosome (CMTlC) 17,81.
Recently, most of CMTlA, most of sporadic CMT1,
and a rare case of complete translocation trisomy 1?p
syndrome with a demyelinating neuropathy were
found to have a D N A duplication on chromosome
1 7 ~ 1 1 . 2[4, 9-1 I f . The CMTlA duplication was demonstrated to be a tandem repeat of 1.5 megabase (Mb)
of DNA {121. In the case of trisomy 17p syndrome,
the translocation breakpoint was mapped to a region
on chromosome 17pl1.2, proximal to the duplication
breakpoint in CMTIA. A gene dosage effect of a gene
or genes within the duplication has been considered to
explain how the duplication o n chromosome 1 7 ~ 1 1 . 2
leads to the CMTlA phenotype C131.
Peripheral myelin protein 22 (PMP-22) gene was
initially identified as a growth arrest-specific (gas-3)
gene expressed in serum-starved fibroblasts [14j, and
later shown to encode a myelin protein (PAS-IIISR13)
expressed in the peripheral nerve 151. Analysis of the
duplication on chromosome 17pl1.2 in CMTlA using
fluorescent in situ hybridization, pulse field gel electrophoresis, and yeast artificial chromosomes has shown
that the CMTl A duplication contains entirely the
PMP-22 gene [I 3, 161. Based on its chromosomal location within the CMTlA duplication, it has been suggested that increased gene dosage of PMP-22 is the
mechanism for CMTIA. However, altered expression
of PMP-22 in CMTlA with D N A duplication encompassing the PMP-22 gene has never been reported.
In this study, we examined the possibility of increased expression of messenger RNA (mRNA) for
From the *Department of Neurology, Osaka University Medical
School, Osaka, and the tDepartrnent of Pediatrics and Dentistry,
Akita University School of Medicine, Akita, Japan.
A&lress correspond~nceto Dr Yoshikawa, Department of Neurology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka
565, Japan.
Received Aug 10, IYqj, and in revised form Sep IS. Accepted for
publication Sep 16, 1993.
Copyright 0 1994 by the American Neurological Association 445
7 a b h I . Clinical Features of Putients with Cbavcot-Marie-Tooth iCMTi Di.reaJe i 1-3).
Patients with Other Demyelinuting Neuroputhie.r (6-10), and Control Siihjeils (1 1-1 3)
Patient
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
Age
( yr)
Duration
of Illness
Sex
40
15
4
5
30
9
Clinical
Diagnosis
38
57
M
F
49
M
CMT
CMT
CMT
CMT
CMT
DNUE
Uremia
CIDP
Paraproteinemia
DNUE
Cardiom yopathy
Leukemia
Leukemia
=
demyelinaring neuropathy of unknown etiology; CIDP
52
24
12
41
64
49
61
54
67
58
AD = autosomal dominant; DNUE
ropathy; ND = nor done.
F
F
F
M
F
M
M
M
M
( yr)
M
2
7
2
1
PMP-22 in biopsied nerves of t h e patients with
CMTlA who had PMP-22 g e n e duplication. For this
purpose, we used N o r t h e r n blot analysis and compared
t h e expression of mRNA for PMP-22 with that of
patients having other demyelinating neuropathies.
Moreover, w e examined t h e biopsied nerves morphologically to explore any relationship between nerve
pathology and altered expression of m R N A s for PMP22 and protein 0 (PO), t h e most abundant myelin protein in t h e peripheral nervous system (PNS). T h e result of this investigation has b e e n published in abstract
form { 171.
Materials and Methods
Patients and Control Subjects
Five paticnts with C M T l A (Patients 1-5, Table 1) were selected based on the presence of the duplication of PMP-22
gene by using quantitative Southern blot analysis. All patients
had a clinical piccure characterized by slowly progressive distal muscle weakness or muscle atrophy, foot deformity, and
areflexia. The mean motor conduction velocity of'the median
nerve was decreased to 20 c 7 (standard deviation) m/sec.
In 3 of 5 patients, there was a family history of a similar
disorder having an autosomal dominant mode of inheritance.
Another 5 patients with various demyelinating peripheral
neuropathics (Patients 6-10, see Table 1) were selected bccause of the absence of the duplication of PMP-22 or because
of the established diagnosis of acquired diseases. Whole or
fascicular specimens of the s u r d nerves or the cutaneous
branch of the superficial peroneal nerves had been obtained
under local anesthesia from both groups of patients.
Histologically normal peripheral nerves were obtained
within 6 hours postmortem from 3 autopsy cases who did
not have clinical evidence of neuropathy in their life histories
or medical records (I'atients 11-13, see Table 1).
446 Annals of Neurology Vol 35 No 4 April 1994
Duplication
of PMP-22
+
+
+
+
+
~
Sporadic
AD
AD
Sporadic
AD
-
ND
ND
ND
-
-
-
ND
-
ND
ND
=
Heredity
-
-
~
-
chronic inflammatory demyelinating polyneu-
Southern Blot AnaLysis
Genomic D N A was extracted from peripheral blood lymphocytes from 6 patients and biopsied skeletal muscles from
1 patient by a standardized method. The D N A was digested
with a restriction enzyme BamHI (Takara Schuzo). Digested
D N A was fractioned on 0.7% agarose gels and transferred
to a Hybond-N nylon membrane (Amersharn). The filters
were prehybridized in 6 x standard saline citrate (SSC), 5 x
Denhardt's solution, 0 . 5 F sodium dodecyl sulfate (SDS),
100 Kgiml of salmon sperm DNA, and 50% formamide for
2 hours at 42"C, and hybridized with {j2P)labeledprobes in
the same solution for 16 hours at 42°C. They were washed at
room temperature in 2 x SSC containing 0.1 ?4; SDS, further
washed for 30 minutes at 56°C in the same buffer, and exposed to X-ray film (X-OMAT-AR, Kodak) at - 70°C.
Human PMP-22 complementary D N A (cDNA) [ 181 was
digested with BstEII and a 0.6-kb fragment was used as the
probe to detect the duplication of PMP-22. Human musclespecific phosphoglycerate mutase (PGAM) gene locatcd on
chromosome 7 1191 was digested with PstI and BstEII, and
a 1.7-kb fragment was used as an internal control. Gene dosages in the patients were determined by densitometric scanning of the hybridization signals using a microcomputer imaging device (Imaging Research, Ontario, Canada). The copy
number of PMP-22 gene was calculated by comparing the
signals obtained from the PMP-22 probe with the signals
from the PGAM probe between patients with CMTlA and
control subjects.
Northern Blot Analyszs
Total RNA was extracted from frozen peripheral nerves of
the patients according to the method of Chomczynski and
Sacchi [20], electrophoresed on 1% agarose gel containing
formaldehyde and transferred to a nylon membrane Filters
were prehybridized in 6 x SSC, 5 x Denhardt's solution,
0 5% SDS, 10 pg/ml of salmon sperm DNA, and 5057 for-
mamide for 2 hours at 42"C, and hybridized with ["P)labeled probes for 16 hours at 42°C. They were washed at
room temperature in 2 x SSC containing 0 . 1 2 SDS, further
washed for 30 minutes at 65°C in the same buffer, and exposed to x-ray films.
The blot was first hybridized with the human PMP-22
cDNA, stripped and rehybridized with the human PO cDNA
[2 I), and then stripped and rehybridized again with the human beta-actin cDNA (Amersham) as a reference probe to
ensure the integrity o f the filter.
Denritomrtric Analysis of Northern Blot
Quantitative analysis was performed by densitometric scanning of appropriate autoradiograms using the microcomputer
imaging device. The relative mRNA expression of PMP-22
or PO in patients with CMT1 A, those with other demyelinating neuropathies, and normal control subjects was calculated
as the ratio of PMP-22 or PO against beta-actin, and the
relative ratios of PMP-22 or PO in patients with CMTlA
or other demyelinating neuropathies were calculated against
normal control subjects by setting the ratio for normal control subjects as 1. The statistical difference between CMTlA
and other neuropathies was determined using two-tailed Student's t test for unpaired samples (957{ confidence limits).
Morpholngirul Study und Regression Analy.ris
A part of the biopsied nerve specimen from each patient and
control subject was fixed in 2.5% glutaraldehyde in 0.05 M
phosphate buffer ( p H 7.4)at 10°C and subsequently osmicared. To evaluate the pathological alterations, teased fibers
were prepared and 100 teased fibers were graded according
to the criteria of Dyck and associates [22). Transverse semithin sections of epoxy-embedded nerves were stained with
thionin blue and were used for measurement of fiber densities under light microscopy. The density of myelinated fibers
(MFs) per square millimeter of endoneurial area was measured on enlarged monitor images at a final magnification of
x 1,000 by computer-assisted image processor Nexus 6400
(Nexus, Tokyo, Japan). Correlations between fiber density
and some variables, that is, age, duration of illness, and relative expression of PMP-22 or PO in each patient of both
groups, were examined using Pearson's coefficient of correlation.
Result
Southern Blot Analysis
BamHI-digested Southern blot analysis using PMP-22
c D N A as a probe revealed a 8.8-kb fragment. Densitometric analysis of the 8.8-kb fragment demonstrated
that three dosages of PMP-22 g e n e were present in
CMTlA patients and two dosages, in patients with
other demyelinating neuropathies and normal control
subjects.
Northern Blot Analysis
Since t h e content of extracted mRNA from individual
biopsied nerves varied (2-4 pg), each sample was hybridized for PMP-22, PO, and beta-actin on t h e same
filter serially, with beta-actin as a reference for direct
F i g 1 . Representatiiae iVurthern blot ana1ysi.c of me.c.renger RNAs
from the biopsied z e w e of a patient umith Charcot-n,larie-Tooth
type 1A (CMT), the binp.ried nen'e o f a patient in the other demydinating neuropathies group (disease rontroli, and the arrtop.tied nerve of a patient without neuropathy (normal control).
The blot uus first hybridized with the peripherul myelin protein
22 (PMP-22) ppobe. then stripped and rehybridized successiue~
with protein 0 (POI and beta-actin probes. N o t e that the autoradiogruphic signal of the PMP-22 probe in CM?' shous higher
density than a979 other signals.
comparison (Fig 1).T h e m e a n relative ratio of PMP-22
mRNA expression in CMTlA (1.73 i. 0.56) against
normal control was significantly higher than that in
o t h e r demyelinating neuropathies (1.09 2 0.24) ( p <
0.05). However, there was n o statistical difference in
t h e mean relative ratio of PO mRNA expression between t h e m (Fig 2).
Morphological AnaLyis
The nerves from the patients with CMTlA showed
m u c h higher frequency of demyelination, remyelination, or both and possessed less density of MFs than
Yoshikawa et ai: Elevated PMP-22 Expression in CMTlA
447
Table 2. Patholonical Findzrms of Biopsied N e m e ~
Graded Pathological
Abnormalities of
Teased Fibersa
0
C
Q)
l
n
Patient
No.
0
a
L
P
6
z
CT
E
1
2
3
4
5
2.0
0
0
c
0
._
u)
T
u)
6
a,
L
+ *
Q
X
a,
>
._
+
c, D, F
0
8
5
0
0
78
51
100
0
92
95
0
0
100
0
3
E
~
L
m
A, B
Fiber
Density
( fimm')
1 .o
7
E
a,
ir
9
10
-
2.0
-
1.0
-
Other demyelinating
neuropathies
I
I
CMTl A
I
Other dernyelinating
neuropathies
Fig 2. Comparison of the relatiw expression of messenger K N A
(mRNA) for PO (A)and PMP-22 (Bi genes in ChawotMarie-Tooth type 1A (CMTI A) and other demyelinating new
ropathies (disease control). See text for explanation of the relative
expression of mRNA.Therc uus a statistically significant d&&ence in PMP-22 expression between the t w o grozrps ip < 0.05).
448 Annals of Neurology
74
80
15
20
11
0
"Definitions of conditions A to F are from Dyck and assnciares [22).
A = normal; B = myelin wrinkling; C = demyelination; D =
demyelination and remyelination; E = axonal degeneration; and F
= remvelinatioti.
A
3.0
7
I
1
CMT1A
2
8
1 0
0
m
-
97
20
42
1,300
2,200
6,100
8,600
1,000
6,900
2,100
4,500
5,900
4,900
Vol 35 No 4
April 1994
did those of patients with other demyelinating neuropathies (Table 2). T o examine the relationship between
PMP-22 or PO mRNA expression and the degree of
pathological alterations, we plotted the relative ratio of
PMP-22 or PO mRNA expression against the density
of MFs in each patient. The data showed a positive
linear relationship ( p < 0.05) between them, with a
higher expression of PMP-22 (Fig 3) or PO mRNA in
nerves with more MFs. More importantly, however,
patients with CMTlA had more PMP-22 mRNA expression than did patients with other demyelinating
neuropathies in nerves with the same fiber density (see
Fig 3), while PO mRNA expression did not show such
a tendency (data not shown). This implies that the
difference of PMP-22 mRNA expression between
CMTlA and other demyelinating neuropathies is not
due to the difference of fiber density between them.
There was a correlation between the density of MFs
and the duration of illness in C M T l A ( r = -0.84, p
< 0.05).
Discussion
This study provided direct evidence that nerves of the
patients with CMT 1A carrying the duplication of PMP22 gene had an elevated expression of PMP-22 mRNA
in comparison with those of patients with other demyeh a t i n g neuropathies. In contrast, PO mRNA expression was not altered in either group. The difference in
mRNA expression between PMP-22 and PO is most
likely derived from a gene dosage effect of PMP-22.
Recently, Chance and coworkers [23} demonstrated
another example of a gene dosage effect of PMP-22
in patients with hereditary neuropathy with liability to
pressure palsies (HNPP), where they found deletion
of chromosome 1 7 ~ 1 1 . 2encompassing the gene for
7500
h
E
E.
-
k
x
.%
5000
C
a,
n
L
a,
0
u.
2500
1.o
2.0
The relative expression of PMP-22
Fig 3. Regression a n a l p s shoudng finear relationship betweepi
the remaining fiber densit3 and the relative messenger RNA
imRNAi expression of PIZIP-22 gene in Charcot-Marie-Tooth
tppe 1A (CMTlA) (r = 0.98. p < 0.01) and other dernyefinating neuropathier (disease control) ir = 0.71. p < 0.051. A t
the same fiber density, PMP-22 mRNA expression was higher
in CMTIA than in diieuse control.
PMP-22. Although the expression of PMP-22 mRNA
in nerves of the patients with HNPP has never been
examined, it is likely that an overexpression or underexpression of PMP-22 is responsible for the phenotype
of CMTlA or HNPP, respectively. Although there are
some similarities of nerve pathology between CMTl A
and H N P P with demyelination and redundant myelin
products (so-called “tomacula” in HNPP) [24, 251,
they are different in the preponderance of onion-bulb
formation and tomacula and in natural history. Nevertheless, it is possible that an abnormal PMP-22 expression results in a defect in maintenance of myelin and
secondary axonal degeneration in both diseases [26].
PMP-22 is a novel glycoprotein recently described
and characterized C271, and the human PMP-22 gene
was sequenced by Hayasaka and colleagues { 181. This
protein was previously designated PAS-I1 in bovine
{28}, gas-3 in mouse [14], and SR13 in rat [lj]. PMP22 is mainly found in the PNS, predominantly in the
compact portion of the myelin sheath of MFs. Analysis
of the PMP-22 amino acid sequence revealed four hydrophobic stretches that might function a? the transmembrane domains, thus making PMP-22 an integral
membrane protein [26]. Pareek and coworkers [29]
recently demonstrated that PMP-22 in myelin is N-
glycosylated and suggested that PMP-22 plays some
role in the compaction of the myelin sheath. But the
biological role of PMP-22 is still unknown.
The trembler (Tr) mouse carries an autosomal dominant point mutation in the PMP-22 gene [30), and
another point mutation affecting PMP-22 gene has
been found in the allelic trembler-J (Tr-J) mouse { 3 11.
Tr and Tr-J mice show limb paralysis, tremor, transient
seizures, as well as severe PNS-specific hypomyelination and continuous Schwann cell proliferation [ 3 2 ] . It
is conceivable that point mutations of PMP-22 demonstrated in the mutant mice may disturb the putative
structural function of PMP-22 resulting in hypomyelination. The point mutation of PMP-22 identical to that
in the Tr-J mouse has been detected in a CMTlA
family in which no DNA duplication was found [331.
It has been suggested that normal PMP-22 expression is necessary in cellular growth arrest during normal development ClSl. Given that PMP-22 serves a
function to regulate Schwann cell division, an overexpression of PMP-22 mRNA, as seen in patients with
CMTlA, therefore may fail to sustain Schwann cell
proliferation after demyelination, leading to disturbed
remyelination or onion-bulb formation. Since segmental demyelination in CMTl A patients is considered to
be secondary to maldevelopment of axons, axonal atrophy, or both in CMTl patients, according to the findings of nerve pathology [34, 351, further studies are
needed to clarify the role of altered expression of
PMP-22 mRNA for the mechanism of demyelination
and onion-bulb formation in CMTlA.
This work was supported by grants for Specific Disease and for
Congenital Disorders from the Ministry of Health and Welfare,
Japan.
References
1. Dyck PJ, Chance PF, Lebo R, Carney JA. Hereditary motor
and sensory neuroparhies. In: Dvck PJ, Thomas PK, Griffin
JW, er al, eds. Peripheral neuropathy. 3rd ed. Philadelphia: WB
Saunders, 1993:1094-1136
2. Iiarding AE, Thomas PK. The clinical fearures of hereditary
motor arid sensory neuropathy types I and 2. Brain 1080;103:
259-280
3. Vance JM, Nicholson GA, Yamauka LH, et al. Linkage of Charcot-Marie-Tooth neuropathy type l a t o chromosome 17. Exp
Neurol 1989;104:186-189
’I. Lupski JR, de Oca-Luna RM, Slaugenhaupt S, er al. D N A duplication associated with Charcot-Marie-Tooth disease type 1A.
Cell 1991;66:2 19-232
5 . Bird TU, Ott J, Giblett ER. Evidence for linkage of CharcotMarie-Tooth neuropathy to the Duffy locus on chromosome I.
Am J H u m Gener 1982;34:388-394
6. Leho RV, Chance PP, Dyck PJ, et al. Chromosome 1 CharcotMarie-Tooth disease (CMTIB) locus in the Fcr receptor gene
region. H u m Genet 1991;88:1-12
7. Chance PP, Bird TI>,O’Connell P, e t al. Genetic linkage and
heterogeneity in type 1 Charcot-Marie-Tooth disease (hereciit x y motor and sensory neuropathy type I). Am J H u m Genet
1990;17:915-925
Yoshikawa et al: Elevated PMP-22 Expression in CMTlA
449
8. Chance PF, Matsunami N, Lensch W, er al. Analysis of the
DNA duplication 1 'pl1.2 in Charcot-Marie-Tooth neuropathy
type 1 pedigrees: additional evidence for a third autosomai
CMTl locus. Neurology 1992;42:2037-%04 1
9. Raeymaekers P, Tinmerman V, Nelis E, et al. Duplication in
chromosome l i p l l . 2 in Charcot-Marie-'Tooth neuropathy type
l a (CMT la). Neurornuscul Disord 1991;1:93-9?
10. Hoogendilk JE, Hensels GW, Gahreels-Festen AAWM. er al.
De-novo mutation in hereditary motor and sensory neuropathy
type 1. Lancer 1992;339:1081-l082
11. Chance PF. Bird T D , Matsunarni N, e t al. Trisomy l i p associated with Char~or-Marie-Toothneuropathy typc l a phenotype:
evidence for gene dosage as a mechanism in CMTlA. Neurology 1992;42:2295-2299
12. Pentao L, Wise CA, Chinault AC, ct al. Charcot-hlarie-Tooth
type 1A duplication appears to arise from recombination at
repeat sequences flanking the I . SMb monomer unit. Nature
Genet 1992;2:292-300
13. Patel PI, Roa BB. Welcher AA, et al. The gene for the peripheral myelin protein PMP-22 is a candidate fur Charcot-klarieTooth disease type I A . Nature Genet 1932;1:159-16>
14. Manfioletti G, Ruaro ME, Sal GU, et al. A growth arresr-specific
(gas) gene codes for a membrane protein. Mol Cell Biol 1990;
10:2924-2930
15. Welcher AA, Suter U, De Leon M ,et id. A myelin protein is
encoded by the homologue of a growth arrest-specific gene.
Proc Natl Acad Sci USA 1991;X8:7195-7199
16. 'limmerman V. Nelis E, Van Hul W, et al. The peripheral myelin protein gene PMP-22 is contained within the CharcotMarie-Tooth disease type 1A duplication. Nature Genet 1992;
1:171-175
1;. Yoshikawa H, NishimuraT. Nakatsuji Y, et al. Elevated expression of mRNA for peripheral myelin protein-22 In biopsied
peripheral nerves of patients with Charcot-~~aric-Tootl~
disease
type 1A. Ann Neurol 1993;34:267 iAbsrracti
18. Hayasaka K, Hinioro M,Kanao K, er al. I d a t i o n and sequence
derermination of cDNA encoding PMP-22(PAS-II!'SR13/GAS3 ) of human peripheral myelin. Biochcm Biophys Res Commun
1992; 186:827-83 1
19. Edwards YH, Sakoda S,Schon E, Povey S. The gene for human
muscle-specific phosphoglycerate murase, PGAM2, mapped to
chromosome 7 by polymerase chain reaction. Genomics 1089;5:
948-951
20. Chornczynski P, Sacchi N. Single-step method o f RNA isolation
b y acid guanidinium thiocyanate-phenol-chloroformextraction.
Anal Biocheni 1'187,162:156- 159
21. Hayasaka K, Nakano K, Tahara M, et al. Isolation and sequence
450 Annals of Neurology 1'01 35 No 4 April 1994
determination of cDNA encoding the major structural protein
of human peripheral myelin. Biochem Biophys Res Cornmun
179 I;180:3 13-5 18
22. Dyck PJ, Giannini C, h s A. Pathologic alterations of nerves.
In: Dyck l!J, Thomas PK, Griffin JW, ct al, eds. Peripheral
neuropathy. 3rd ed. Philadelphia: WB Saunders, 1993:514-59>
23. Chance PF, Alderson MK, Leppig KA, e t al. DNA deletion
associated with hereditary neuropathy with liahiliry to pressure
palsies. Cell 1993;72:143-151
24. Yosliikawa H, Fijimura H, Yanagihara T. Focal myelin rhickening in HMSN type 1. J Neuropathol Exp Neurol 1992;51:
347 (Abstract)
25. Yoshikawa H, Dvck PJ. Uncompacted inner myelin kiniellae in
inherited tendency to pressure palsy. J Neuropathol Exp Nrurol
199 I:jO:649-6i 7
26. Surer U. Welcher A, Snipes J. Progress in the molecular understmding (if hereditary peripheral neuropathies reveals new insights into the biology of the peripheral nervous system. Trends
Neurosci 1993;16:50-56
27. Snipes GJ, Suter U, Welcher AA. Shooter EM. Characterization
of a novel peripheral nervous s y w m myelin protein (PIMP-221
SRI1). J Cell B i d 1992:117:225-218
28. Kicamura K, Suzuki hl. Uyeinura K. Purification and partial
characterization o f rwo glycoproteins in bovine peripheral nerve
myelin membrane. Biochim Biaphys Acta 1976;455:806-816
29. Pare& S, Suter U, Snipes GJ. et al. Detection and processing
o f peripheral myelin protein PMP22 in cultured Schwann cells.
.I B i d Chem 19')i;2(,8:10372--10179
30. Suter U, Welcher AA, Ozceiik T. et a]. Trembler mouse carries
a point mutation in a myelin gene. Nature 1992;3>6:241-244
11. Suter U, Moskow JJ, Welcher AA, e t a]. A leucine-to-proline
mutation in putative first transmcmhrane domain of the 22-kDa
peripheral myelin protein in the rrembler-J mouse. Proc Natl
Acad Sci USA 199.?;89:4382-4386
32. Henry EW, Cowen JS, Sidman RL. Comparison of trembler
arid trembler-J mouse phenotypes: varying severity of peripheral
hypomyelination. .I Neuropathol Exp Neurol 1983;42:688-:06
33. Valentijn LJ, Baas F, Wolterman RA, et al. Identical point mutarions of PMP-22 in trembler-J mouse and Charcot-Marie-Tooth
disease type 1A. Nature Genet 1992;2:288-291
34. Pvieier C, Maibach R, lsler W, Bischoff A. Dynamic aspects of
peripheral nerve changes in progressive neural muscular atrophy. Light- and electron-microscopic studies of serial nerve biopsies.J Neurol 1976:211:111-124
35. Nukada H, Dyck PJ, Karnes JL. Thin axuns relative to myelin
spirnl length in hereditary motor and sensory neuropathy, type
1. Ann Neurol 1983;14648-655
Документ
Категория
Без категории
Просмотров
0
Размер файла
553 Кб
Теги
expressions, biopsies, periphery, patients, rna, nerve, messenger, charcot, toots, typed, disease, marie, protein, elevated, myelin
1/--страниц
Пожаловаться на содержимое документа